Our goal is to collaborate with the Simbios Center to develop a theoretical framework to predict and quantify important post-stroke hemiparetic walking impairments from spatiotemporal measurements in the clinic,, test and enhance the computational algorithms being developed in the Simbios simulation tool kit (SimTK), and provide a powerful suite of new analysis tools to broaden its scope and application. Aim 1 will use SimTK to generate subject-specific simulations to determine how different subjects with hemiparesis (n=20) increase their fastest comfortable walking speed following locomotor-therapy intervention. These simulations, which will emulate measured walking kinematics, kinetics and muscle activity pre- and post-intervention, will be analyzed to relate spatiotemporal walking characteristics (e.g., step length asymmetry, or ratio of paretic to non-paretic step lengths) to specific motor impairments (e.g., poor propulsion or stepping by the paretic leg relative to the non-paretic leg) and to identify the role of individual muscles to these impairments. Clinicians will then be able to use spatiotemporal measurements in the clinic to tailor locomotor retraining to specifically address the root causes of impaired ambulation for an individual and monitor her/his progress during rehabilitation to improve outcomes more efficiently. Aims 2-3 will i) integrate into SimTK the biomechanical modeling and simulation tools developed by us to analyze muscle function and coordination during human movement;ii) provide a rich database of clinical data, dynamic models and simulations for the Simbios repository, and iii) assist the simulation community in developing a standard framework for analyzing impaired walking across a diverse range of clinical populations. This project will establish a powerful collaboration and exploit existing synergies between our research group and the Simbios Center to advance the national infrastructure in neuromuscular biomechanics and related biomedical domains, and will assist us in our efforts to develop subject-specific simulations to understand the motor impairments and muscle coordination deficits limiting walking performance and hindering efficient and effective therapy for persons with post-stroke hemiparesis.